Variant rs10872670 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005100.4(AKAP12):c.349A>G(p.Lys117Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,590,998 control chromosomes in the GnomAD database, including 474,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.76 ( 42023 hom., cov: 21)

Exomes 𝑓: 0.78 ( 432837 hom. )

Consequence

AKAP12
NM_005100.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.442

Variant links:

Genes affected

AKAP12 (HGNC:370): (A-kinase anchoring protein 12) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

AKAP12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.87914E-7).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP12	NM_005100.4 link	c.349A>G	p.Lys117Glu	missense_variant	4/5	ENST00000402676.7	NP_005091.2	Q02952-1Q86TJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP12	ENST00000402676.7 link	c.349A>G	p.Lys117Glu	missense_variant	4/5	5	NM_005100.4	ENSP00000384537.2		Q02952-1

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

110917

AN:

146178

Hom.:

41997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.714

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.809

Gnomad ASJ

AF:

0.822

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.801

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.782

Gnomad OTH

AF:

0.777

GnomAD3 exomes

AF:

0.754

AC:

186973

AN:

248104

Hom.:

71091

AF XY:

0.748

AC XY:

100370

AN XY:

134180

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.828

Gnomad ASJ exome

AF:

0.825

Gnomad EAS exome

AF:

0.595

Gnomad SAS exome

AF:

0.658

Gnomad FIN exome

AF:

0.787

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.781

GnomAD4 exome

AF:

0.776

AC:

1121038

AN:

1444722

Hom.:

432837

Cov.:

AF XY:

0.772

AC XY:

555037

AN XY:

718520

show subpopulations

Gnomad4 AFR exome

AF:

0.716

Gnomad4 AMR exome

AF:

0.827

Gnomad4 ASJ exome

AF:

0.834

Gnomad4 EAS exome

AF:

0.700

Gnomad4 SAS exome

AF:

0.657

Gnomad4 FIN exome

AF:

0.797

Gnomad4 NFE exome

AF:

0.785

Gnomad4 OTH exome

AF:

0.775

GnomAD4 genome

AF:

0.759

AC:

110995

AN:

146276

Hom.:

42023

Cov.:

AF XY:

0.760

AC XY:

53938

AN XY:

70958

show subpopulations

Gnomad4 AFR

AF:

0.715

Gnomad4 AMR

AF:

0.809

Gnomad4 ASJ

AF:

0.822

Gnomad4 EAS

AF:

0.622

Gnomad4 SAS

AF:

0.659

Gnomad4 FIN

AF:

0.801

Gnomad4 NFE

AF:

0.782

Gnomad4 OTH

AF:

0.778

Alfa

AF:

0.772

Hom.:

85662

Bravo

AF:

0.752

TwinsUK

AF:

0.780

AC:

2894

ALSPAC

AF:

0.773

AC:

2981

ESP6500AA

AF:

0.698

AC:

3076

ESP6500EA

AF:

0.787

AC:

6767

ExAC

AF:

0.747

AC:

90652

Asia WGS

AF:

0.647

AC:

2249

AN:

3476

EpiCase

AF:

0.780

EpiControl

AF:

0.783

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

DANN

Benign

0.60

DEOGEN2

Benign

0.012

T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.16

T;.;T;T

MetaRNN

Benign

7.9e-7

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.46

N;N;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

1.2

N;N;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.015

MPC

0.23

ClinPred

0.0015

GERP RS

2.8

Varity_R

0.032

gMVP

0.015

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over